rs2990510

Variant names:

• chr1-197051528-T-G
• rs2990510
• NM_001994.3:c.1556-649A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001994.3(F13B):​c.1556-649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,994 control chromosomes in the GnomAD database, including 5,507 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5507 hom., cov: 32)
• Consequence: F13B NM_001994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 19 publications found

Genes affected

F13B (HGNC:3534): (coagulation factor XIII B chain) This gene encodes coagulation factor XIII B subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]

F13B Gene-Disease associations (from GenCC):

• factor XIII, b subunit, deficiency of

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13B	NM_001994.3	c.1556-649A>C		intron_variant	Intron 9 of 11	ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.1556-649A>C		intron_variant	Intron 9 of 11	1	NM_001994.3	ENSP00000356382.2
F13B	ENST00000649282.1	c.311-649A>C		intron_variant	Intron 2 of 4			ENSP00000497116.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39350 AN: 151876 Hom.: 5501 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39364 AN: 151994 Hom.: 5507 Cov.: 32 AF XY: 0.257 AC XY: 19073 AN XY: 74282

African (AFR) AF: 0.158 AC: 6557 AN: 41496

American (AMR) AF: 0.255 AC: 3876 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3468

East Asian (EAS) AF: 0.130 AC: 669 AN: 5164

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3243 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21452 AN: 67948

Other (OTH) AF: 0.264 AC: 555 AN: 2106

Alfa AF: 0.298 Hom.: 12694

Bravo AF: 0.251

Asia WGS AF: 0.222 AC: 770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2990510; hg19: chr1-197020658;